Hetero Diels–Alder Reactions with a Dicationic Urea Azine Derived Azo Dienophile and Their Use for the Synthesis of an Electron‐Rich Pentacene

Abstract Herein, the first hetero Diels–Alder (DA) reactions with a stable, dicationic urea azine derived azo dienophile, synthesized by two‐electron oxidation of a neutral urea azine are reported. Several charged DA products were synthesized in good yield and fully characterized. The DA adduct of anthracene is in thermal equilibrium with the reactants at room temperature, and the reaction enthalpy and entropy were determined from the temperature‐dependent equilibrium constant. Furthermore, base addition to solutions of the pentacene DA product led to deprotonation, cleavage of the N−N bond, and formation of an electron‐rich 6,13‐bisguanidinyl‐substituted pentacene. The redox and optical properties of this new pentacene derivative were studied. Furthermore, the dication resulting from its two‐electron oxidation was synthesized and fully characterized. The results disclose a new elegant route to electron‐rich pentacene derivatives.


Synthesis of the Diels-Alder dienophile 1(BF4)2
Using an upscaled, slightly modified procedure we achieved higher yields compared with the previously published procedure. [1] 1,2-bis(1,3-dimethylimidazolidin-2-ylidene)-hydrazine [1] (750 mg, 3.34 mmol, 1 eq.) and 1.00 g of NOBF4 (1.00 g, 8.69 mmol, 2.6 eq.) are mixed in a Schlenk tube and dissolved in acetonitrile (30 mL), resulting in an immediate colour change to red-brown. While stirring, the reaction vessel is evacuated numerous times (at least 8 times) until the solvent started to boil and then purged with Ar to remove traces of NO. Then, the reaction mixture is stirred 16 h under slightly reduced pressure. Subsequently, all volatiles are removed in vacuo and the residue is dissolved in acetonitrile (8 mL) and crystallized by diffusion of diethyl ether (30 mL) from the gas-phase into the solution. The product 1(BF4)2 is obtained as red needles (1.24 g, 3.11 mmol, 93%).

General procedure for the dicationic hetero Diels-Alder reaction of 1(BF4)2 with different dienes
The dicationic hetero Diels-Alder reaction is carried out by adding the dienophile 1(BF4)2 (1 eq.) and corresponding diene (1 eq.) in a Schlenk tube. After the addition of acetonitrile, the reaction mixture is stirred for the given reaction time (reaction progress can be followed by decolorization of the red reaction mixture). After the work-up, XRD suitable single crystals are grown.

Tetracene Diels-Alder product, 4(BF4)2
The reaction is carried out by the general procedure with 1(BF4)2 (400 mg, 1.01 mmol, 1 eq.) and tetracene (230 mg, 1.01 mmol, 1 eq.) under exclusion of light in MeCN (30 mL) for 36 h. Subsequently the reaction mixture is filtered under Ar, all volatiles are removed in vacuo from the filtrate and the residue is washed with Et2O (3x3 mL) and ice cooled acetone (2x5 mL), yielding the title compound as an off-white powder (337 mg, 538 µmol, 53%). XRD suitable single crystals are obtained by diffusion of Et2O from the gas-phase into a MeCN solution.

Pentacene Diels-Alder product 5(BF4)2
The reaction is carried out by the general procedure with 1(BF4)2 (400 mg, 1.01 mmol, 1 eq.) and pentacene (280 mg, 1.01 mmol, 1 eq.) under exclusion of light in MeCN (30 mL) for 72 h. Subsequently the reaction mixture is filtered under Ar, all volatiles are removed in vacuo from the filtrate, and the residue is washed with Et2O (3x3 mL) and ice cooled acetone (2x5 mL), yielding the title compound as an off-white powder (527 mg, 780 µmol, 77%). XRD suitable single crystals are obtained by diffusion of Et2O from the gas-phase into a MeCN solution.

6,13-Bis(N,N'-dimethylethyleneguanidinyl)-pentacene, 7
In a Schlenk tube, 5(BF4)2 (100 mg, 147.9 µmol, 1 eq.) and KOtBu (34 mg, 303.1 µmol, 2.05 eq.) are mixed. After addition of THF (4 mL) a green suspension formed, that is stirred for 22 h under exclusion of light. Subsequently the reaction mixture is filtered and the residue is dried. The raw product is washed under Ar with THF (3x4 mL). Then, it is suspended in DCM and washed with water (3x4 mL) (filtering under Ar) to remove KBF4. Unfortunately, it is not possible to remove all KBF4 due to its low solubility. Please note that the reaction does not work with LiOtBu in place for KOtBu, indicating that the formation of un-soluble KBF4 might be an important driving force. The title compound is obtained as an emerald coloured powder (35 mg, 70 µmol, 47%).  In a Schlenk tube 7 (15 mg, 30 µmol, 1 eq.) is suspended in THF (4 mL) under the absence of light trifluoromethanesulfonic acid (6 µL, 63 µmol, 2.1 eq.) is added. The reaction mixture immediately changes colour from a green suspension to a deep blue purple solution. It is stirred for a period of 5 min. Then all volatiles are removed in vacuo and the residue is washed with Et2O (2x3 mL). For the growth of XRD suitable single crystals, the purple residue is dissolved in MeCN (2.5 mL) and stored at −18 °C.
The reaction was also done with HCl (2 Molar solution in Et2O, 20 µl, 2.1 eq) for this reaction 7 (10 mg, 20 µmol, 1eq.) was dissolved in MeCN. The reaction mixture was stirred for a period of 5 min. Then all volatiles are removed in vacuo and the residue is washed with Et2O (2x3 mL). The blue purple residue was used directly for UV-Vis measurements.

NMR analysis of the DA products
The DA products were investigated by 1 H, 13 C NMR as well as 2D-NMR and 1 H NOESY experiments to elucidate their structure in solution (see SI). The 1 H NMR (400 MHz, d3-MeCN) spectrum of the butadiene adduct 2(BF4)2 contains four singlet signals at  = 3.97 (4 H), 3.78 (8 H), 3.04 (12 H) and 1.71 (6 H) ppm. The first two downfield shifted signals are broadened and belong to the methylene bridge and guanidinyl ethylene backbone. Structural conformation is further confirmed by the 1 H NOESY NMR showing correlation through space for the four guanidinyl CH3 groups with the CH2 ring atoms as well as with the guanidinyl ethylene backbone. Furthermore, the methyl groups attached to the six-membered ring show correlation through space with the CH2 ring atoms, too. The signal broadening is caused by either rotation or inversion of the guanidinyl groups in solution which cannot be resolved on the NMR time scale, leading to similar chemical shifts for all CH3 and CH2 protons in the 1 H NMR spectra.
The 13 C NMR spectrum of 3(BF4)2 contains eleven signals from which nine arise from carbon atoms connected to protons. These carbons bound directly to protons are assigned with the aid of 1 H-13 C HSQC spectra (see SI). All carbon atoms in the former cyclopentadiene moiety are chemically inequivalent, while for the guanidinyl moieties some carbon atoms are equivalent on the NMR time scale. For example, there are two quaternary carbon signals for the central guanidinyl carbons but only two instead of four signals for the connected methyl and the ethylene groups. The compound should therefore exhibit C1 symmetry in solution and the urea azine moiety on top of the cyclopentene ring adopts a trans conformation as seen in the crystal structure. Chemical equivalence for the guanidinyl backbone (methyl groups and ethylene bridge) could be established through rotation about the CN azine-guanidine bond. Flipping inversion at the azine N atoms of the guanidinyl groups can probably be ruled out due to the inequival ence of the carbon signals of the two guanidinyl groups.
The 1 H NMR spectrum of the pentacene-DA product 5(BF4)2 shows four signals for the twelve aromatic protons, one signal for the two CH-bridge atoms with a characteristic shift of 6.41 ppm and two signals for the four guanidinyl methyl groups, as well as two complex multiplets for the ethylene bridge of the guanidinyl moiety. The compound presumably exhibits C2 symmetry in solution giving a structure in which the guanidinyl groups again adopt trans-conformation (as in the crystal structure), for which half of the atoms are chemically equivalent. Interestingly, from 1 H NOESY NMR we find direct chemical exchange for the guanidinyl protons in which the methyl groups interconvert. Similar spectra are obtained for the tetracene adduct.  Table 4.1) relied on the law of mass conservation. Absolute concentrations in the equilibrium were estimated with the aid of the internal standard hexamethylbenzene (HMB c = 8.14 mM, 1 and anthracene at a concentration of 30 mM) by integration of respective peak signals for anthracene (A), the dienophile 1 and the Diels-Alder product 6. In order to obtain more accurate concentrations, integration and speciation was carried out with the MestreNova internal module Mnova qNMR. [3] The peak areas were deconvoluted in cases where they overlapped with other signals (accuracy of integration ±5%, errors estimated by error convolution).  The different solubility of the diene and dienophile component used in our reactions might hamper the analysis over a wide temperature regime. Anthracene is only partially soluble in MeCN in concentrations required for an NMR experiment, [4] while the dicationic dienophile is completely dissolved. In less polar solvents the opposite behaviour is found. For estimation of the equilibrium constant we therefore used a mixture of CD3CN:CDCl3 (1:1) to which an internal standard (hexamethylbenzene, 8.14 mM) was added. Evaluation of the thermodynamic parameters relied on a Van´t Hoff plot (ln(Keq) vs. 1/T). For the full temperature region from −40 to +55 °C, a linear fit proved to be inadequate. The Van´t Hoff plot is linear on the assumption that the enthalpy and entropy are temperature-independent in the analysed temperature region. However, it is known that in some cases ΔH and ΔS vary significantly with temperature. [5] Deviations from the linear behaviour could be caused, for example, by a temperature-dependent conformational change or secondary equilibria such as solubility.

Room-temperature reversible hetero Diels-Alder reaction of 6(BF4)2:
[5c] Analytical expressions for the temperature-dependence are usually based on the change of heat capacity during a reaction. Then, a polynomial fit is used to account for a non-constant reaction enthalpy (see Figure 4.
Alternatively, the thermodynamic data could be derived from a linear fit for the higher temperature region (+25 to +55 °C), yielding a reaction enthalpy ΔH = −47 ± 5 kJ mol −1 and a reaction entropy ΔS = −135 ± 15 J mol −1 K −1 . Table 5.1. Selected structural parameters (bond lengths in Å, angles in °, α dihedral angle between the two guanidinyl planes, β dihedral angle between the planes of the two carbon sites of the diene in the DA compound) of the DA products as well as 1red and 1(BF4)2.

Selected structural parameters of the DA products 2-5
Averaged values are given in cases with two independent molecules in the unit cell or two bonds of the same type.
Compound (6) 1.326 (6) 1.554 (6) 1.508 (6) 1.514 (6) 1.538 (6) 1.326 (3)   The wave marked by an asterisk is due to O2 reduction. Therefore, we assume that the wave observed in the cyclic voltammogram belongs to a quasi-reversible two-electron redox process. The quasi-reversible nature indicates that there should be only a small structural change between the neutral and dicationic redox state. [6] This is in accordance with the DFT calculations showing only small changes for the critical parameters between the calculated structure of 7 and crystal structure of 8. No formation of a butterfly conformation was observed upon oxidation, and the acene moiety is only slightly twisted. A related compound, 1,4-bis-tetramethylguanidinyl-benzene, was investigated earlier by our group. [7] The CV spectra show one quasi-reversible two-electron redox process (E1/2 = −0.18 V vs. Fc/Fc + in DCM), ΔE = 180 mV). The lower redox potential of 7 is in accordance with the more electron-rich acene bridge. about 525 nm as well as the NIR bands disappeared in the UV-Vis spectra (in comparison with the spectra for 1.00 eq. AgSbF6). The colour of the solution now changed from red to yellow. According to TD-DFT calculations for 7 •+ , the lowest energy transition is located in the NIR region at 1337 nm, and the second lowest energy transition is located at 544 nm (see also Figure 7.2). The very broad absorption in the NIR might be composed of more than one band. The lower-energy band is tentatively assigned to a charge resonance (CR) band, originating from the class III or borderline class III/II mixed-valence (MV) system. [8] (Alternatively, it is due to an enlarged πsystem resulting from dimer formation of neutral 7 with its radical monocation 7 •+ . [9] ) The second lowest energy transition is also in good accordance with the observed shoulder at 525 nm. All attempts to isolate a salt of the radical 7 •+ failed, underlining its instability towards disproportionation to the dicationic and neutral redox states. Nevertheless, the results argue for a two-step oxidation process (two oneelectron steps) as also found for amino-tetracene and amino-anthracene derivatives. [8c,10] Differential pulse voltammetry showed for amino-tetracene and amino-anthracene derivatives that the observed quasi-reversible single wave voltammogram consists of two successive reversible one-electron oxidation steps with a minuscule potential difference of ΔE = 40 mV and ΔE = 60 mV, respectively.

Titration of 7 with
In relation to our work we want to note the work by Ito et al. on the synthesis and redox properties of various diamino-acenes. [6,10] In summary these systems represent Wurster-type redox systems characterised by three distinct redox states. TMPD, the precursor to the radical denoted Wurster's blue, is a well-known representative. [11] However as shown by Ito et al., by enlarging the π-system of the bridge between the two redox sites, the two step oxidation process is not necessarily preserved, as structural differences in the oxidised form might induce a change to a single two-electron process (with inverted oxidation potentials) and also might affect the electrochemical reversibility.  Further evidence for the presence of a radical form 7 •+ is provided by EPR experiments. The EPR spectrum of a solution containing 7 and 0.5 or 1.0 eq. of AgSbF6 in DCM shows a broad paramagnetic signal (g = 2.0029) (see Figure 8.1). Hyperfine splitting is almost unresolved, but the free electron is expected to predominantly couple with two nitrogen cores adjacent to the pentacene moiety, therefore one would expect a quintet signal (not resolved). Interestingly investigation of the filtrate obtained from the reaction of the pentacene DA product 5 and LDA in THF shows a similar but better resolved paramagnetic signal (g = 2.0020) and a second signal (g = 2.0150) (Figure 8.2). Preparation of the EPR probe under air or measuring of the probe after about a day leads to vanishing of the second signal and broadening of the first signal (g = 2.0029) while the hfs is still visible (Figure 8.3). Observation of a paramagnetic signal for the reaction of 5(BF4)2 'with KOtBu/LDA to give 7 indicates oxidation to 7 •+ , probably due to a competing redox reaction with 1 accompanied by retro Diels-Alder reaction:

Computational data
Ionic Diels-Alder reactions are quite rare in chemistry. They compromise reactions with positively or negatively charged ionic species as diene or dienophile component. [12] The ionic nature is preserved along the reaction coordinate until formation of the ionic cycloadduct. [12e] In the last years several theoretical studies have been devoted to the mechanism of ionic DA reactions. [12d,e,13] In these studies, different mechanisms have been proposed for DA reactions of non-charged and charged species. By inspection of the transition state structures, correlations between the experimental reaction rates and the global charge transfer were disclosed. In our case the solvent effect is significant due to the charge of +2 of the dienophile. Therefore, some preliminary investigations were carried out on the influence of the solvent on the thermodynamics as well as kinetics of the herein described ionic DA reactions. Diene, dienophile and DA product were optimised at the B3LYP+D3/def2-TZVP level of theory and the solvent effect was estimated by singlepoint calculations with the conductor-like screening model (COSMO) for the solvent acetonitrile (εr = 37.5). The calculated thermodynamic data, collected in Table 9 The calculations also explain the experimental result that no DA reaction occurs with the dienes furan and pyrrole. Additionally, they highlight that for anthracene, for which a chemical equilibrium is found at room temperature, the position of the equilibrium depends on the relative solvent permittivity (the solvent polarity). Qualitative information about the reaction kinetics could be derived from the Frontier Molecular Orbital (FMO) theory. According to the FMO theory (considering only electronic interactions between HOMO/LUMO in the rate-determining TS), the reaction rate of the DA reaction is proportional to the interaction energy of the HOMO and LUMO orbitals of diene and dienophile. [14] The interaction energy depends on the degree of favourable orbital overlap as well as the energy difference between the frontier orbitals. [15] For a normal electron demand DA reaction the HOMO of the nucleophilic diene and the LUMO of the electrophilic dienophile are of relevance. Furthermore, one would expect the rate to increase with the size of the acene. We can say that for the best-soluble acene in this series, anthracene, the rate is high as the equilibrium quickly (<5 min) responds to temperature changes. However, one would expect the reactions with the larger acenes to be even faster. Here the poor solubility might be the limiting factor.
Another point is the competition between DA pathway and an electron transfers (redox) pathway. As the dienes become more electron rich an electron transfer might be favoured. The competing redox pathway is also influenced by the solvent as the LUMO energy of the dienophile depends on the solvent polarity.   . 1(BF4)2). Note that butadiene stands for 2,3-dimethylebutadiene.    The structure of neutral 7 was calculated at B3LYP+D3/TZVP level of theory. The comparison between the calculated structure of 7 and that obtained by SCXRD for (7+2H) 2+ (see Figure 10.1) shows that both structures are similar, deviating only in some bond lengths.

TD-DFT calculations, vertical transitions
Interestingly in the protonated form the two guanidinyl groups are located in a plane almost perpendicular to the pentacene ring plane (see Figure 10.2a). In the oxidised form the guanidinyl groups are twisted about 90° (see Figure 10.2b). While we find a planar acene structure for the protonated form, the oxidised form shows a slightly twisted acene structure. Furthermore, the angle between the acene carbon and the guanidinyl group (∠(C11-C1-N1)) is larger than 120°.
These observations are in line with earlier studies by our group on the structural parameters of 1,4-bis(tetramethylguanidinyl)benzene. [7] For the oxidised form we also found a bent-twisted structure, in which the nitrogen atom establishes π-interactions with the carbon π-system as well as the CN2 group of the guanidinyl group.